Three enzymes which are involved in the metabolism of the nucleoside bases will be the targets of inhibitor studies: cytidine deaminase, adenosine deaminase, and carbamyl phosphate synthetase II. With cytidine deaminase, we will investigate the kinetics and mode of inhibition of our phosphorus-containing pyrimidine transition state analog, which we have already demonstrated to be the most potent inhibitor known for this enzyme. For application to adenosine deaminase, the analogous phosphorus-containing purine derivatives will be evaluated. A series of multi-substrate analogs for carbamyl phosphate synthetase will be studied. The deaminase inhibitors may shed light on the mechanism of action of these enzymes, as well as act in a synergistic manner with a number of clinically important anti-neoplastic agents. Selective inhibitors of carbamyl phosphate synthetase could prove to have useful anti-cancer activity in their own right.